BACKGROUND Epidemiologic studies suggest a strong link between poor habitual sleep quality and increased cardiovascular disease risk. However, the underlying mechanisms are not entirely clear. Metabolomic profiling may elucidate systemic differences associated with sleep quality that influence cardiometabolic health. METHODS We explored cross-sectional associations between sleep quality and plasma metabolites in a nested case-control study of coronary heart disease (CHD) in the Women's Health Initiative (WHI; n = 1956) and attempted to replicate the results in an independent sample from the Nurses' Health Study II (NHSII; n = 209). A sleep-quality score (SQS) was derived from self-reported sleep problems asked in both populations. Plasma metabolomics were assayed using LC-MS with 347 known metabolites. General linear regression was used to identify individual metabolites associated with continuous SQS (false-discovery rate <0.05). Using least absolute shrinkage and selection operator (LASSO) algorithms, a metabolite score was created from replicated metabolites and evaluated with CHD risk in the WHI. RESULTS After adjusting for age, race/ethnicity, body mass index (BMI) and smoking, we identified 69 metabolites associated with SQS in the WHI (59 were lipids). Of these, 16 were replicated in NHSII (15 were lipids), including 6 triglycerides (TAGs), 4 phosphatidylethanolamines (PEs), 3 phosphatidylcholines (PCs), 1 diglyceride (DAG), 1 lysophosphatidylcholine and N6-acetyl-L-lysine (a product of histone acetylation). These metabolites were consistently higher among women with poorer sleep quality. The LASSO selection resulted in a nine-metabolite score (TAGs 45: 1, 48: 1, 50: 4; DAG 32: 1; PEs 36: 4, 38: 5; PCs 30: 1, 40: 6; N6-acetyl-L-lysine), which was positively associated with CHD risk (odds ratio per SD increase in the score: 1.16; 95% confidence interval: 1.05, 1.28; p = 0.0003) in the WHI after adjustment for matching factors and conventional CHD risk factors. CONCLUSIONS Differences in lipid metabolites may be an important pathogenic pathway linking poor habitual sleep quality and CHD risk.

中文翻译：

---

绝经后妇女的习惯睡眠质量，血浆代谢产物和冠心病风险。

背景技术流行病学研究表明，不良的习惯性睡眠质量与增加的心血管疾病风险之间存在密切的联系。但是，其潜在机制尚不完全清楚。代谢组学分析可以阐明与睡眠质量相关的系统差异，这些差异会影响心脏代谢健康。方法我们在妇女健康倡议组织（WHI; n = 1956）的冠心病（CHD）巢式病例对照研究中探讨了睡眠质量与血浆代谢产物之间的横断面关联，并尝试在独立的样本中复制结果护士健康研究II（NHSII； n = 209）。睡眠质量评分（SQS）来自两个人群中自我报告的睡眠问题。使用LC-MS与347种已知代谢物分析血浆代谢组学。使用一般线性回归来确定与连续SQS相关的单个代谢物（错误发现率<0.05）。使用最小绝对收缩和选择算子（LASSO）算法，从重复的代谢物创建代谢物评分，并在WHI中用CHD风险进行评估。结果在调整了年龄，种族/民族，体重指数（BMI）和吸烟后，我们在WHI中鉴定出69种与SQS相关的代谢产物（59种是脂质）。其中16个在NHSII中复制（15个是脂质），包括6个甘油三酸酯（TAG），4个磷脂酰乙醇胺（PEs），3个磷脂酰胆碱（PC），1个甘油二酸酯（DAG），1个溶血磷脂酰胆碱和N6-乙酰基-L-赖氨酸（组蛋白乙酰化的产物）。这些代谢产物在睡眠质量较差的女性中始终较高。LASSO选择产生9个代谢物得分（TAG 45：1，48：1，50：4; DAG 32：1; PEs 36：4，38：5; PCs 30：1，40：6; N6-乙酰-L-赖氨酸），与匹配因素和常规冠心病风险调整后，在WHI中与冠心病风险呈正相关（得分比每SD增加的比值：1.16； 95％置信区间：1.05，1.28； p = 0.0003）因素。结论脂质代谢产物的差异可能是联系不良的习惯性睡眠质量和冠心病风险的重要致病途径。